Previous studies from this laboratory have shown that prenatal exposures to TOK R (2,4-dichloro-phenyl-p-nitrophenyl ether) induces neonatal mortality in rats. Affected newborns become cyanotic, exhibit labored breathing and expire shortly after birth. Effects of exposure on lung maturation were examined insofar as lungs of newborns were hypoplastic and incompletely expanded prior to death. Histological, physiologic and biochemical evaluations of fetal, neonatal and adolescent lungs indicated that the lung is not the target organ for TOK-induced neonatal mortality. Recent findings have indicated that exposed fetuses have heart malformations involving ventricular septal defects and obstruction of the pulmonary outflow tract. The cyanosis and incomplete expansion of lungs are believed to be related to these heart malformations. Future studies will be directed toward: full characterization of heart malformations in exposed fetuses; 2) determination of whether a dose-response relationship exists for occurrence of specific heart malformations; 3) examination of whether maternal anoxia is induced by TOK exposures which causes the heart malformations; and 4) examination of cellular and biochemical events in embryonic hearts immediately after TOK exposure.